The Genetic Architecture of Congenital Diarrhea and Enteropathy
Zeenat Gaibee, Neil Warner, Katlynn Bugda Gwilt, Wenjuan Li, Rui Guan, Michael Yourshaw, Ryder Whittaker Hawkins, Christiane Zorbas, Jonathan St. Germain, Mahdi Tabatabaie, Suli Mao, Vered Pinsk, Baruch Yerushalmi, Lee-kai Wang, Stanley F. Nelson, Laura J. Wozniak, Dror S. Shouval, Manar Matar, Amit Assa, Nathaniel Frost, Lissette Jiménez, Sari Acra, Thomas Walters, Stephen Mouat, Michael Li, Denis L. J. Lafontaine, Matthew J. Tyska, Brian Raught, Yaron Avitzur, Wayne I. Lencer, James R. Goldenring, Martín G. Martín, Jay R. Thiagarajah, Aleixo M. Muise
Abstract
BACKGROUND: Next-generation sequencing has enabled precision therapeutic approaches that have improved the lives of children with rare diseases. Congenital diarrhea and enteropathies (CODEs) are associated with high morbidity and mortality. Although treatment of these disorders is largely supportive, emerging targeted therapies based on genetic diagnoses include specific diets, pharmacologic treatments, and surgical interventions. METHODS: We analyzed the exomes or genomes of infants with suspected monogenic congenital diarrheal disorders. Using cell and zebrafish models, we tested the effects of variants in newly implicated genes. RESULTS: . CONCLUSIONS: We have characterized the broad genetic architecture of CODE disorders in a large case series of patients and identified three novel genes associated with CODEs. (Funded by the National Institutes of Health and others.).